title: Transplantation of encapsulated hepatocytes during acute liver failure improves survival without stimulating native liver regeneration.
abstract: The aim of this study was to evaluate the effects of intraperitoneal transplantation of encapsulated human hepatocytes on liver metabolism and regeneration of mice with acute liver failure. Primary human hepatocytes were immortalized using lentiviral vectors coding for antiapoptotic  genes and microencapsulated using alginate-polylysine polymers. In vitro, immortalized human hepatocytes showed low, but stable, synthetic and catabolitic functions over time, when compared to primary hepatocytes. In vivo, mice with acute liver failure and transplanted with encapsulated immortalized  human hepatocytes had a significantly improved survival and biochemical profile, compared to mice transplanted with empty capsules. Serum levels of cytokines implicated in liver regeneration were lower in mice transplanted with hepatocytes compared to mice receiving empty capsules. This decrease  was significant for IL-6 and HGF at 3 h. Measurement of liver regeneration showed no significant difference between mice transplanted with hepatocytes compared to control groups. Intraperitoneal transplantation of encapsulated immortalized hepatocytes significantly improved survival of mice  with acute liver failure by providing metabolic support and without modifying liver regeneration. The lower levels of cytokines implicated in liver regeneration suggest that the metabolic support provided by the encapsulated hepatocytes reduced the inflammatory stress on the liver and herein  decreased the regenerative trigger on residual hepatocytes. These data emphasize that metabolic function and regeneration of hepatocytes are two distinct aspects that need to be studied and approached separately during acute liver failure.
authors.affiliation: Surgical Research Unit, Department of Surgery, University Hospital Geneva, Geneva, Switzerland.
authors.forename: Antonino
authors.initials: A
authors.lastname: Sgroi
authors.forename: Gang
authors.initials: G
authors.lastname: Mai
authors.forename: Philippe
authors.initials: P
authors.lastname: Morel
authors.forename: Reto M
authors.initials: RM
authors.lastname: Baertschiger
authors.forename: Carmen
authors.initials: C
authors.lastname: Gonelle-Gispert
authors.forename: Véronique
authors.initials: V
authors.lastname: Serre-Beinier
authors.forename: Leo H
authors.initials: LH
authors.lastname: Buhler
mesh_terms: D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D002214:Capsules / Q000737:chemistry; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D016207:Cytokines / Q000097:blood; D017228:Hepatocyte Growth Factor / Q000097:blood; D022781:Hepatocytes / Q000166:cytology* / Q000637:transplantation; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008099:Liver / Q000502:physiology; D017114:Liver Failure, Acute / Q000378:metabolism / Q000401:mortality / Q000628:therapy*; D008115:Liver Regeneration; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012709:Serum Albumin / Q000378:metabolism; D015996:Survival Rate; D014183:Transplantation, Heterologous
chemical_list: D002214:Capsules; D016207:Cytokines; D015850:Interleukin-6; D012709:Serum Albumin; D017228:Hepatocyte Growth Factor; D001219:Aspartate Aminotransferases; D001663:Bilirubin